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Clinical features of and genetic predisposition to drug-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in a single Korean tertiary institution patients—investigating the relation between the HLA -B*4403 allele and lamotrigine

  • Pharmacogenetics
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Abstract

Purpose

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but fatal adverse mucocutaneous reactions to certain drugs. Recent studies suggest that ethnicity and genetic predisposition may play a crucial role in the manifestation of the reaction. In this study, we described the role of human leukocyte antigen (HLA)-B alleles in the development of clinical characteristics and treatment outcomes of SJS/TEN in a single Korean tertiary hospital.

Methods

We retrospectively reviewed the medical records (from March 1, 2010 to February 28, 2014) of 30 patients diagnosed with SJS and/or TEN.

Results

The main causative drugs were anticonvulsants (26.7 %) and allopurinol (26.7 %), followed by antibiotics (16.7 %), acetazolamide (10.0 %), acetaminophen (10.0 %), and herbal medication (6.7 %). The mean latencies of these drugs were variable. Liver damage was the most common symptom (observed in 63.3 % of the patients). Of the five patients with lamotrigine-induced SJS/TEN, three expressed the HLA-B*4403 allele (60.0 %). Of the seven patients with allopurinol-induced SJS/TEN, five expressed the HLA-B*5801 allele (71.4 %).

Conclusions

The major SJS/TEN-inducing drugs were found to be allopurinol and anticonvulsants (such as lamotrigine). We speculated that Korean individuals expressing the HLA-B*4403 allele may be highly susceptible to lamotrigine-induced SJS/TEN.

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Acknowledgments

This research was supported by a grant from Ministry of Food and Drug Safety to operation of the regional pharmacovigilance center in 2014.

Conflict of interest

None declared.

Source of funding

None declared.

Authors’ contributions

H.J. Park (MD): craft7820@yuhs.ac

The first author generated and analyzed the data, prepared the manuscript draft, and approved the final version of the manuscript.

S.R. Kim (MD): sungryul0782@yuhs.ac

This author actively participated in data collection and approved the final version of the manuscript.

D.W. Leem (MD): tokepler@yuhs.ac; I.J. Moon (MD): niljoo@yuhs.ac; B.S. Koh (MD): nicolass@yuhs.ac; and K.H. Park (MD): white182@yuhs.ac

These authors consolidated the clinical data used in the study and approved the final version of the manuscript.

J-W. Park (MD, PhD): parkjw@yuhs.ac

This author conceptualized the study, interpreted the data, revised intermediate drafts, and approved the final version of the manuscript.

J-H. LEE (MD, PhD): jhleemd@yuhs.ac

The corresponding author of this article provided valuable inputs to the study, analyzed and interpreted the data, and revised and approved the final version of the manuscript.

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Authors and Affiliations

  1. Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, South Korea

    Hye Jung Park, Sung Ryeol Kim, Dong Woo Leem, Il Joo Moon, Beom Seok Koh, Kyung Hee Park, Jung-Won Park & Jae-Hyun Lee

  2. Severance Hospital Regional Pharmacovigilance Center, Seoul, South Korea

    Hye Jung Park, Kyung Hee Park, Jung-Won Park & Jae-Hyun Lee

  3. Division of Allergy and Immunology, Department of Internal Medicine, Severance Hospital Regional Pharmacovigilance Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea

    Jae-Hyun Lee

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  1. Hye Jung Park
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Park, H.J., Kim, S.R., Leem, D.W. et al. Clinical features of and genetic predisposition to drug-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in a single Korean tertiary institution patients—investigating the relation between the HLA -B*4403 allele and lamotrigine. Eur J Clin Pharmacol 71, 35–41 (2015). https://doi.org/10.1007/s00228-014-1764-0

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